The Scripps Research Institute

Scripps Clinic and Research Foundation

Sorrento Therapeutics, Inc.

Kim D Janda

Richard A Lerner

Peter Wirsching

Jonathan W Lockner

Sydney Brenner

Nicholas T Jacob

Richard J Ulevitch

Hicham Fenniri

Vladimir Kravchenko

Changshou Gao

Samuel J Danishefsky

Dale L Boger

Francis Xavier Tavares

Benjamin F Cravatt

Gunnar F Kaufmann

Alfonso Tramontano

Alan Saven

Michael M Meijler

Alexander V Mayorov

Brunhilde Felding-Habermann

Diane Schloeder

Shoji Ikeda

Jon A Ashley

Armando Cordova

Hyunsoo Han

Junguk Park

Eric P Zorrilla

Peter K Vogt

There are disclosed imidazolinopyrimidinone compounds that have activity to induce TRAIL gene expression in macrophages. There is further disclosed a method for treating various cancers comprising administering effective amounts of an imidazolinopyrimidinone having the structure of Formula I herein.

Pharmacophore for trail induction

An improved heroin conjugate vaccine is detailed; to accomplish this task the systematic exploration of twenty vaccine formulations with varying combinations of carrier proteins and adjuvants were undertaken. In regard to adjuvants, a Toll-like receptor 9 (TLR9) agonist and a TLR3 agonist in the presence of alum were explored. The vaccine formulations containing TLR3 or TLR9 agonist alone-elicited strong anti-heroin antibody titers and blockade of heroin-induced antinociception when formulated with alum; however, a combination of TLR3 and 9 adjuvants did not result in improved efficacy. Investigation of stability of the two lead formulations revealed that the TLR9 but not the TLR3 formulation was stable when stored over 30 days. Furthermore, mice immunized with the TLR9+alum heroin vaccine gained significant protection from lethal heroin doses, suggesting that this vaccine formulation is suitable for mitigating the lethal effects of heroin, even following long-term storage at room temperature.

Heroin vaccine

There is disclosed a compound, a pharmaceutical composition and a method of cancer treatment with an improved Myc inhibitor compound. More specifically, there is disclosed an improved compound having with improved solubility, improved binding characteristics and better efficacy and therapeutic activity inhibiting c-MYC wherein the improved compound comprises a tri-substituted pyridine having a thiazoyl moiety at position Rversus an earlier disclosed genus of tri-substituted pyridine structures.

Compounds for MYC inhibition

Fentanyl is an addictive prescription opioid that is over 80 times mora potent than morphine. The synthetic nature of fentanyl has enabled the creation of dangerous 'designer drug' analogues that escape toxicology screening, yet display comparable potency to the parent drug. Alarmingly, a large number of fatalities have been linked to overdose of fentanyl derivatives. Herein, we report an effective immunotherapy for reducing the psychoactive effects of fentanyl class drugs. A single conjugate vaccine was created that elicited high levels of antibodies with cross-reactivity for a wide panel of fentanyl analogues, Moreover, vaccinated mice gained significant protection from lethal fentanyl doses. Lastly, a surface plasmon resonance (SPR)-based technique was established enabling drug specificity profiling of antibodies derived directly from serum. Our newly developed fentanyl vaccine and analytical methods may assist in the battle against synthetic opioid abuse.

Synthetic opioid vaccine

This invention provides small molecule Myc-inhibitors. Also provided in the invention are therapeutic applications of these compounds for treating Myc-driven cancer and other related methods.

Small molecule c-Myc inhibitors

In this study, we capitalized on the antimicrobial property and low oral bioavailability of known salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen. The anthelmintics displayed excellent potency againststrains 630 and 4118 (with MIC values as low as 0.06-0.13 &#x3bc;g/mL for rafoxanide) via a membrane depolarization mechanism, interestingly, closantel, rafoxanide and compound 8 were bactericidal against logarithmic- and stationary-phase cultures of the BI/NAP1/027 strain 4118. Further evaluation of the salicylanilides showed their preferential activity against Gram-positive over Gram-negative bacteria. Moreover, the salicylanilides were non-hemolytic and were non-toxic to mammalian cell lines HepG2 and HEK 293T/17 within the range of their in vitro MICs and MBCs. The salicylanilide anthelmintics exhibit desirable bactericidal and pharmacokinetic properties and are amenable to repositioning as anti-agents.

Methods for treatment ofinfections

The invention provides chiral haptens (&#x2212;)-3'-AmNic and (&#x2212;)-N4N for use in generating antibodies in a patient specific for (&#x2212;)-nicotine. The haptens can be conjugated to suitable carrier proteins and administered as an antigenic mixture, optionally comprising adjuvant(s), to a patient suffering from nicotine or tobacco addiction or habituation.

Enantiopure haptens for nicotine vaccine development

There are disclosed imidazolinopyrimidinone compounds that have activity to induce TRAIL gene expression in macrophages. There is further disclosed a method for treating various cancers comprising administering effective amounts of an imidazolinopyrimidinone having the structure of Formula I herein. The invention is directed, in various embodiments, to a compound and pharmaceutical composition comprising an effective amount of a compound capable of inducing expression of TRAIL gene in cells capable of expressing the TRAIL gene to produce the cytokine TRAIL.

The invention is directed to methods of inducing apoptosis, arresting cell cycle, or inhibiting cellular proliferation, or any combination thereof, in a tumor cell, by administration of an effective amount of an N-acyl homoserine lactone analog (AHL), optionally in conjunction with a tumor modulating agent such tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) to the patient. Novel bioactive analogs of an N-acyl homoserine lactone are also provided.

Trail enhancers for the selective killing of cancer cells

Immunoconjugates for impeding weight gain and treating obesity in a subject are disclosed. The immunoconjugates comprise a ghrelin mimetic polypeptide hapten, a spacer moiety comprising one of more polyethylene glycol (PEG) units, and a protein carrier moiety. Immunoconjugates optionally include a conjugation moiety for conjugating the polypeptide hapten with a linker moiety or the protein carrier moiety and a linker moiety for conjugating the conjugation moiety with the protein carrier moiety.

Ghrelin mimetic polypeptide hapten immunoconjugates having improved solubility and immunogenicity and methods of use thereof

The invention features immunoconjugates for impeding weight gain and treating obesity in a subject. The immuno-conjugates comprise particular ghrelin polypeptides and a suitable carrier moiety.

Vaccines and methods for controlling adiposity

The invention provides an immunogenic molecular entity, a supramolecular assembly, and an antibody that can be used to inhibit Gram-positive bacterial quorum sensing, prevent infection or development of a disease condition associated with a Gram-positive bacterial infection. The invention also provides methods of inhibiting Gram-positive bacterial quorum sensing, and methods of preventing infection or development of a disease condition associated with a Gram-positive bacterial infection.

Antibody-mediated disruption of quorum sensing in bacteria

This invention generally relates to methods of producing an antibody phage population having affinity for a tumor cell target expressing a metastatic phenotype. The invention further relates to antibody compositions that specifically bind to a cell surface receptor on the metastatic cell.

Growing community of inventors

La Jolla, CA, United States of America

Kim D Janda